US12102680B2ActiveUtilityA1

Anti-TIGIT antibodies

Assignee: MERCK SHARP & DOHME LLCPriority: Aug 19, 2014Filed: May 15, 2020Granted: Oct 1, 2024

Est. expiryAug 19, 2034(~8.1 yrs left)· nominal 20-yr term from priority

Inventors:Sybil M. G. Williams Drake Laface Laurence Fayadat-Dilman Gopalan Raghunathan Linda Liang Wolfgang Seghezzi

C07K 2317/56C07K 2317/73C07K 2317/565A61K 45/06A61K 39/3955C07K 16/2803C07K 16/2818C07K 2317/74C07K 2317/21C07K 2317/92C07K 2317/76C07K 2317/52C07K 2317/34C07K 2317/24A61K 2039/507A61K 2039/505C07K 16/28Y02A50/30A61P 43/00A61P 37/04A61P 37/02A61P 35/00A61P 31/00A61K 39/39541

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Claims

Abstract

The present invention relates to anti-TIGIT antibodies, as well as use of these antibodies in the treatment of diseases such as cancer and infectious disease.

Claims

exact text as granted — not AI-modified

The invention claimed is:

1. A method of treating a human subject with cancer in need thereof, comprising administering to the subject an effective amount of a monoclonal antibody or antigen binding fragment thereof that binds to human TIGIT, wherein the monoclonal antibody and antigen binding fragment thereof comprise a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:88, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:89, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:90, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:91, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:92, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:93,
optionally in association with a further therapeutic agent or therapeutic procedure.

2. A method of treating a human subject having an infection or infectious disease, comprising administering to the subject an effective amount of a monoclonal antibody or antigen binding fragment thereof that binds to human TIGIT, wherein the monoclonal antibody and antigen binding fragment thereof comprise a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:88, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:89, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:90, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:91, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:92, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:93,
optionally in association with a further therapeutic agent or therapeutic procedure.

3. A method of treating a human subject with cancer in need thereof, comprising administering to the subject an effective amount of a monoclonal antibody or antigen binding fragment thereof that binds to human TIGIT, wherein the monoclonal antibody and antigen binding fragment thereof comprise a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:88, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:134, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:90, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:91, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:92, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:93.

4. The method of claim 3 , wherein the monoclonal antibody and antigen binding fragment thereof comprise:
a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:128 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:132;
b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:127 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:130;
c) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:128 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:133;
d) a heavy chain variable region comprising at least 97% identity to SEQ ID NO: 128 and a light chain variable region comprising at least 97% identity to SEQ ID NO: 132, wherein any sequence variations occur in the framework regions of the monoclonal antibody;
e) a heavy chain variable region comprising at least 97% identity to SEQ ID NO:127 and a light chain variable region comprising at least 97% identity to SEQ ID NO: 130, wherein any sequence variations occur in the framework regions of the monoclonal antibody; or
f) a heavy chain variable region comprising at least 97% identity to SEQ ID NO:128 and a light chain variable region comprising at least 97% identity to SEQ ID NO: 133, wherein any sequence variations occur in the framework regions of the monoclonal antibody.

5. The method of claim 1 , wherein the monoclonal antibody and antigen binding fragment thereof comprise a heavy chain variable region comprising at least 97% identity to the amino acid sequence of SEQ ID NO: 94 and a light chain variable region comprising at least 97% identity to the amino acid sequence of SEQ ID NO:95.

6. The method of claim 3 , wherein the monoclonal antibody and antigen binding fragment thereof comprise two heavy chains and two light chains.

7. The method of claim 3 , wherein the monoclonal antibody comprises a human IgG1 constant domain and a human kappa constant domain.

8. The method of claim 7 , wherein the human IgG1 constant domain comprises SEQ ID NO: 86 and the human kappa constant domain comprises SEQ ID NO: 56.

9. A method of treating a human subject having an infection or infectious disease, comprising administering to the subject an effective amount of a monoclonal antibody or antigen binding fragment thereof that binds to human TIGIT, wherein the monoclonal antibody and antigen binding fragment thereof comprise a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:88, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:134, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:90, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:91, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:92, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:93.

10. The method of claim 9 , wherein the monoclonal antibody and antigen binding fragment thereof comprise:
a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:128 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:132;
b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:127 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:130;
c) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:128 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:133;
d) a heavy chain variable region comprising at least 97% identity to SEQ ID NO:128 and a light chain variable region comprising at least 97% identity to SEQ ID NO: 132, wherein any sequence variations occur in the framework regions of the monoclonal antibody;
e) a heavy chain variable region comprising at least 97% identity to SEQ ID NO: 127 and a light chain variable region comprising at least 97% identity to SEQ ID NO: 130, wherein any sequence variations occur in the framework regions of the monoclonal antibody; or
f) a heavy chain variable region comprising at least 97% identity to SEQ ID NO:128 and a light chain variable region comprising at least 97% identity to SEQ ID NO: 133, wherein any sequence variations occur in the framework regions of the monoclonal antibody.

11. The method of claim 3 , wherein the monoclonal antibody and antigen binding fragment thereof comprise a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:128 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:132.

12. The method of claim 9 , wherein the monoclonal antibody and antigen binding fragment thereof comprise a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:128 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:132.

13. The method of claim 12 , wherein the monoclonal antibody and antigen binding fragment thereof comprise a human IgG1 constant domain comprising SEQ ID NO: 86 and a human kappa constant domain comprising SEQ ID NO: 56.

14. A method of treating a human subject with cancer in need thereof, comprising administering to the subject (a) an effective amount of a monoclonal antibody that binds to human TIGIT and (b) an effective amount of pembrolizumab, wherein the monoclonal antibody comprises two heavy chains and two light chains;
wherein each of the heavy chains comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; and
wherein each of the light chains comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO:132.

15. The method of claim 14 , wherein the monoclonal antibody comprises a human IgG1 constant domain and a human kappa constant domain.

16. The method of claim 15 , wherein the human IgG1 constant domain comprises SEQ ID NO: 86 and the human kappa constant domain comprises SEQ ID NO: 56.

17. The method of claim 16 , wherein the cancer is lung cancer.

18. The method of claim 17 , wherein the cancer is non-small cell lung cancer.

19. A method of treating a human subject with cancer in need thereof, comprising administering to the subject (a) an effective amount of a monoclonal antibody that binds to human TIGIT and (b) an effective amount of pembrolizumab,
wherein the monoclonal antibody comprises two heavy chains and two light chains; and
wherein the monoclonal antibody comprises a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:88, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:134, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:90, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:91, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:92, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:93.

20. The method of claim 19 , wherein the monoclonal antibody comprises a human IgG1 constant domain and a human kappa constant domain.

21. The method of claim 20 , wherein the human IgG1 constant domain comprises SEQ ID NO: 86 and the human kappa constant domain comprises SEQ ID NO: 56.

22. The method of claim 21 , wherein the cancer is lung cancer.

23. The method of claim 22 , wherein the cancer is non-small cell lung cancer.

24. The method of claim 8 , wherein the cancer is lung cancer.

25. The method of claim 24 , wherein the cancer is non-small cell lung cancer.

26. The method of claim 11 , wherein the monoclonal antibody or antigen binding fragment thereof is a monoclonal antibody, wherein the monoclonal antibody comprises two heavy chains and two light chains.

27. The method of claim 26 , wherein the monoclonal antibody comprises a human IgG1 constant domain and a human kappa constant domain.

28. The method of claim 27 , wherein the human IgG1 constant domain comprises SEQ ID NO: 86 and the human kappa constant domain comprises SEQ ID NO: 56.

29. The method of claim 28 , wherein the cancer is lung cancer.

30. The method of claim 29 , wherein the cancer is non-small cell lung cancer.

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